Secondary Outcomes
a. Acute asthma severity score in ED and hospitalized studies:Although all the studies included information for this outcome, they
were analyzed separately according to the setting, type of score, and
how it was reported. The two big trials23,25 done in
the ED included difference in score, without giving the basal or
post-intervention score, precluding the possibility to include their
data in the overall score meta-analysis of ED studies. There was no
significant difference in the asthma score between the budesonide and
the control group in these two trials (Figure 5a). This result was
similar using random effect model (RR=-0.13 [-0.38 to 0.12), p=0.30).
The other four studies done in ED20,22,27,28 reported
post-intervention data; when the data was reported in median and IQR, we
estimated mean and SD according to the literature16.
We found that children from the budesonide group significantly improved
their asthma score compared with the placebo group in the ED
studies20,22,27,28 (SMD: -0.30 [-0.53 to -0.06],
p=0.01, I2=27%), Figure 5b. This result was similar
using random effect model (SMD: -0.31 [-0.60 to -0.02), p=0.04). In
the subanalysis comparing doses of budesonide (≥2mg vs. <2
mg), the pool data of ED studies showed a significant improvement in
acute asthma severity score in the budesonide vs. placebo group, but
clearly this effect was driven by the studies using ≥2 mg (Figure 5c).
Among studies performed in trials with hospitalized children, one
study24 showed a significant differences in the asthma
score at 1 hour, 2 hours and 3 hours from intervention favor to
budesonide vs placebo group (7.36±1.03 vs 9.18±1.01 p<0.01 at
1h, 5.91±0.52 vs 7.30±1.05 p<0.01 at 2 h, 5.42±0.50 6.36±0.70
p<0.01 at 3 h, respectively). The other
trials21,26 only gave graphics but not data on asthma
score. One study21 reported a significantly reduction
in the clinical score for the budesonide, but the
other26 did not.
b. LOS in ED studies: Three studies20,25,28 reported
data for this outcome. There was not significantly difference in LOS
between the budesonide and control groups MD= -0.26 [-0.88 to 0.35];
I2= 91%, p=0.40).
c. Readmissions during follow-up: Four
studies20,21,23,25 included data for this outcome.
There was no significant difference in readmission during the follow-up
(overall OR=0.89 [0.36 to 2.25]; I2 = 0%, p=0.81).
d. Lung function: Only two studies22,24reported this outcome and both measured the peak expiratory flow rate
(PEFR). Nuhoglu et al.22 reported an increased mean of
PEFR in the budesonide vs. placebo group (72.50 ± 23.8 vs. 47.86 ± 18.9,
p=0.02). Similarly, Akhtaruzzaman et al.24 reported
significantly more improvement in the % of predicted PEFR value in the
budesonide vs. placebo group at 1,2 and 3 hour after treatment (76.63 ±
1.4 vs. 69.30 ± 1.1, p=<0.01; 77.42 ± 1.2 vs. 71.42 ± 1.1,
p=<0.01; and 78.58 ± 1.1 vs. 72.36 ± 1.0, p=<0.01,
respectively).
e. SpO2: Four studies done in
ED20, 23,27,28 reported data for this outcome. The
pooled data of two studies23,27 showed no difference
in the mean change from baseline among budesonide vs. control group
(data not shown). Similarly, Sung et al.20 reported no
difference. However, Razi et al.28 showed significant
higher SpO2 at 120 min post-intervention in the
budesonide vs. placebo group (95% [93–98] vs. 91.5% [90–96],
p=0.012).
Among studies performed in trials with hospitalized children,
Akhtaruzzaman et al.24 found a significant difference
at 1, 2, and 3 hrs. after intervention favorable for the budesonide vs.
placebo group (95.15% ± 0.71 vs. 94.12% ± 0.89, p <0.01;
95.55% ± 0.71vs. 94.45% ± 0.83, p<0.01; and 95.94% ± 0.35
vs. 94.76% ± 0.66, p<0.01, respectively).
f. Heart and respiratory rates: Three
studies20,23,28 done at ED and one in hospitalized
children24reported data for heart rate. The pooled
data of two ED studies23,28 showed no significant
difference in overall heart rate change between the budesonide and
control groups (MD = -1.08 [-6.48 to 4.32]; I2 =
0%, p=0.70). Also, Sung et al.20 reported that there
were no differences between groups. The study performed in hospitalized
children24 showed a significant lower heart rate at 1,
2, and 3 hrs. after intervention favorable to budesonide vs. placebo
group (102.18±6.58 vs. 109.09±5.48, p <0.01; 88.42±5.36 vs.
96.85±5.24, p<0.01; 83.64±3.86 vs. 93.52±4.56,
p<0.01, respectively).
Four studies21,23,24,27 reported data for the
respiratory rate. There was no significant change in pooled data for
respiratory rate among studies done in ED23,27 (MD =
0.43 [-1.43 to 2.29]; I2 = 0%, p=0.65). However,
among trials with hospitalized children, Sano et al.21reported significantly higher respiratory rates at 24, 36, and 48 hrs.
among children in the control group (who received ipratropium bromide)
than those in the budesonide group; and Akhtaruzzaman et
al.24 reported a significant lower respiratory rate at
1, 2, and 3 hrs. after intervention favorable to budesonide vs. placebo
group (24.97±3.25 vs. 27.82±4.10, p <0.01; 23.55±2.77 vs.
25.27±3.35,p <0.01; and 22.42±1.79 vs. 24.48±2.74, p
<0.01, respectively).
g. Additional SABA requirement: Only one
study20 reported this outcome, showing no difference
in additional salbutamol use between groups.
h. Adverse events: Six studies20,23-27reported AE data, and four studies20,24,26,27 reported
no occurrence of AEs. Upham et al.23 reported a total
of 106 AEs in 62 patients (33 in the budesonide and 29 in the control
group). Alangari et al.25 described 28 AE episodes, 17
cases of fine tremors (7 in the budesonide and 10 in the control group),
and 11 cases of palpitations (6 in the budesonide and 5 in the control
group); these details were described in their protocol document
(NCT01524198).